Historically, accurate and precise isotope ratios have been measured using magnetic sector-type instruments. Orbital trapping mass spectrometers, such as the Orbitrap™ mass analyzer manufactured by Thermo Fisher Scientific, Inc., have more recently been shown able to provide accurate and precise isotope measurements (“The 100 isotopologue challenge: Orbitrap mass spectrometry as a means of high-dimension clumped and position-specific isotope analysis”, John Eiler, Brooke Dallas, Elle Chimiak, Johannes Schwieters, Dieter Juchelka, Alexander Makarov, Jens Griep-Raming, Poster at ASMS 2016). However, the precision that can be obtained is limited by the number of ions detected, which in turn is limited by the space charge capacity of the ion optical storage elements involved in the mass spectrometer, for example the linear ion trap (C-trap) used for storing ions for injection into the Orbitrap™ mass analyzer. For transient signals, such as from chromatographic separation, typically only a very small fraction of the total number of ions generated in the ion source can be practically used.
For each measurement scan of ions in an orbital trapping mass analyzer, a transient is acquired for several milliseconds (referred to as a detection time, DT). For most applications under consideration, DT is in the order of 250 ms, 500 ms, or even longer. Whilst detection in the orbital trapping mass analyzer is taking place, ions can be collected and stored in an ion storage device for analysis in the next measurement scan. If the ion storage time (IT) is equally long or longer than DT, in general nearly all of the stored ions can be analyzed. Experimental overhead times, such as the time from stopping the ion collection process to injection into the mass analyzer, normally cannot be avoided and therefore modify this calculation slightly. These times are typically negligible compared to an overall cycle time though. However, when chromatographic separation of the sample is used, for instance using a gas chromatograph (GC), IT is usually significantly shorter than DT and it may not then be possible to achieve a sufficient number of scans in the mass analyzer. The result of this may be loss of a significant fraction of the ions produced and consequent reduced overall precision and accuracy of the measured isotope ratios.
Such problems are even more significant for orbital trapping mass analyzers, in which the total number of ions that can be observed in each injection may be limited by space charge effects. No matter how scans are organized, there is a limit in the number of ions observed per second for such analyzers, which cannot be exceeded. This limit may be as a low as 2×104 to 3×104 ions per second. A typical GC peak lasts a few seconds, so in direct elution of peaks, it may not be possible to observe more than 2×105 to 3×105 ions. Often, 107 to 108 ions per measurement must be reached, in order to achieve desirable shot noise limits for common isotopic analyses.
These issues can be addressed with the use of a peak broadening device in-line with a GC column, such as described in the above reference and in a presentation at Clumped Isotope Workshop, January 2016 by John Eiler et al. With reference to FIG. 1, there is schematically shown a known IRMS system with such a peak broadening device in-line with a GC column, operated by a single in-line valve. The IRMS system 10 comprises: an injector 20; a GC column 30; a multi-port switching valve 40; and a peak broadener 50. The injector 20 provides sample input to the GC column 30. The column flow 35 from GC column 30 is provided as a first input to the multi-port switching valve 40. A second input to the multi-port switching valve 40 is coupled to a helium supply 70. A first output of the multi-port switching valve 40 is provided as an input to the peak broadener 50. The output of the peak broadener 50 is provided to the ion source of the mass spectrometer 60, such that the peak broadener 50 is provided in line between the GC column 30 and the mass spectrometer 60. The mass spectrometer 60 is preferably an orbital trapping mass analyzer. The peak broadener 50 can be in the form of a tube or flask. A second output of the multi-port switching valve 40 is provided to a vacuum pump acting as a vent or waste line 80.
This allows the column flow 35 to be provided to the peak broadener 50 and mass spectrometer 60 when a compound (peak) of interest is output, or to be passed to a vent at other times. It can thereby extend the time available for mass spectrometry analysis of sample peaks eluting from the column. As an example, such devices may make peaks last hundreds of seconds (minutes to tens of minutes) to reach desired analytical goals. In this way, a mass analysis of the compound or compounds of interest can be performed without a significant reduction in the number of ions lost (conversely, improving the useful ion yield in the analysis). However, further improvements to the precision and accuracy of isotope ratio measurements using this technique would be desirable.